September 24, 2014
Gilead’s Investigational Tenofovir Alafenamide (TAF)-Based Single Tablet HIV Regimen Meets 48-Week Primary Objective in Two Phase 3 Studies
-- U.S. and EU Filings Planned for Q4 2014 --
“As individuals with HIV are living longer, there is a need for
treatments that are not only highly effective, but also offer an
improved safety profile,” said
In Study 104, 93.1 percent (n=405/435) of patients taking E/C/F/TAF compared to 92.4 percent (n=399/432), of patients taking Stribild, with 95 percent CI from -2.6% to 4.5%, achieved HIV RNA of less than 50 copies/mL at week 48. In Study 111, 91.6 percent (n=395/431) of E/C/F/TAF patients compared to 88.5 percent (n=385/435) of Stribild patients, with 95 percent CI from -1.0% to 7.1%, achieved HIV RNA of less than 50 copies/mL at week 48. Both regimens were generally well tolerated. Discontinuation rates due to adverse events, safety and resistance profiles were comparable between E/C/F/TAF and Stribild in both studies.
Laboratory abnormalities were generally similar for both regimens, with the exception of renal and bone safety indicators, which favored the TAF-based regimen. There was a statistically significant difference in the median change in estimated glomerular filtration rate (eGFR) from baseline to week 48, favoring the TAF-based regimen (-6.8 mL/min for E/C/F/TAF vs. -10.4 mL/min for Stribild in Study 104 (p<0.001); -5.7 mL/min for E/C/F/TAF vs. -11.9 mL/min for Stribild in Study 111 (p<0.001)). Additionally, patients taking the TAF-based regimen experienced a significantly smaller median percentage decrease from baseline in lumbar spine bone mineral density compared to Stribild patients (-1.19 vs. -2.67 in Study 104 (p<0.001); -1.11 vs. -2.81 in Study 111 (p<0.001)) and in hip bone mineral density (-0.77 vs. -3.24 in Study 104 (p<0.001); -0.74 vs. -2.78 in Study 111 (p<0.001)).
In Study 104, median changes from baseline in total fasting cholesterol, HDL (high-density lipoprotein or “good” cholesterol) and LDL (low-density lipoprotein or “bad” cholesterol) were, respectively, 30, 7 and 15 mg/dL for E/C/F/TAF and 12, 3 and 2 mg/dL for Stribild (total cholesterol, p<0.001; HDL, p<0.001; LDL, p<0.001). In Study 111, median changes from baseline in total cholesterol, HDL and LDL were respectively, 27, 7 and 11 mg/dL for E/C/F/TAF and 14, 4 and 2 mg/dL for Stribild (total cholesterol, p<0.001; HDL, p<0.001; LDL, p<0.001).
Gilead plans to submit data from Studies 104 and 111 for presentation to a scientific conference in early 2015.
Several additional ongoing Phase 3 studies are evaluating E/C/F/TAF among multiple HIV patient populations, including patients who switch to E/C/F/TAF from either a single tablet or multi-pill Truvada-containing regimens, patients with a history of antiviral drug resistance, patients with mild to moderate renal impairment and treatment-naïve HIV-positive adolescents. An additional Phase 3b study, WAVES, is evaluating E/C/F/TAF among HIV-positive women who switched from a multi-pill regimen.
Based on the results of Studies 104 and 111 and data from these
additional ongoing studies, Gilead plans to submit regulatory
applications for E/C/F/TAF in the
About the E/C/F/TAF Studies
Study 104 and Study 111 are randomized, double-blind, 96-week clinical trials among 1,744 treatment-naïve HIV-1 infected adults with viral load greater than or equal to 1,000 copies/mL. In Study 104, 867 patients were randomized (1:1) and received E/C/F/TAF (n=435) or Stribild (n=432). In Study 111, 866 patients were randomized (1:1) and received E/C/F/TAF (n=431) or Stribild (n=435).
The primary efficacy endpoint of the studies is the proportion of
patients with viral load < 50 copies/mL at 48 weeks of treatment as
determined by the
The studies are ongoing in a blinded fashion. After week 96, patients will continue to take their blinded study drug until treatment assignments have been unblinded, at which point all will be given the option to participate in an open-label rollover extension and receive E/C/F/TAF. Additional information about the study can be found at www.clinicaltrials.gov.
Elvitegravir, cobicistat and E/C/F/TAF are investigational products in
About Tenofovir Alafenamide
Tenofovir alafenamide (TAF) is a nucleotide reverse transcriptase inhibitor (NtRTI). It is an investigational novel prodrug of tenofovir, the active agent in Viread® (tenofovir disoproxil fumarate), which is also an NtRTI. Phase 1b dose-ranging studies identified a dose of TAF that is ten times lower than Viread. The smaller milligram size of TAF may enable the development of new fixed-dose combinations and single tablet regimens for HIV therapy that are not feasible with Viread.
Elvitegravir is a member of the integrase inhibitor class of
antiretroviral compounds, which interfere with HIV replication by
blocking the ability of the virus to integrate into the genetic material
of human cells. Elvitegravir was licensed by Gilead from
Cobicistat is a cytochrome P450 3A (CYP3A) inhibitor. It boosts blood
levels of the HIV protease inhibitors atazanavir and darunavir by
suppressing CYP3A, an enzyme that metabolizes these drugs in the body.
Cobicistat acts only as a pharmacokinetic enhancer and has no antiviral
activity. Cobicistat is approved under the tradename Tybost®
This press release includes forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995 that are
subject to risks, uncertainties and other factors, including risks
related to its ability to submit regulatory applications for E/C/F/TAF
U.S. full prescribing information including BOXED WARNING for Stribild and Viread is available at www.gilead.com.
Stribild, Tybost, Viread and Vitekta are registered trademarks of
For more information on
Gilead Sciences, Inc.
Patrick O’Brien, 650-522-1936 (Investors)
Cara Miller, 650-522-1616 (Media)